Knuble grew up in Michigan and was drafted by the Detroit Red Wings in 1991. He spent four years at the University of Michigan. He joined the Red Wings for their 1997 Cup victory but did not play enough games to have his name put on the Cup. In 1998, he played 53 games, and though he played only 3 playoff games, he got his name on the Cup when Detroit repeated as champs.

He was traded to the New York Rangers in the offseason, where he played a full season for the first time. At the end of the 2000 season, he was dealt to the Boston Bruins, where he had his breakout season in 2002-03. Playing with superstar Joe Thornton and sniper Glen Murray, Knuble scored 30 goals and 59 points. After the lockout, Knuble signed with the Flyers. In 2005-06 Knuble set career highs with 34 goals, 31 assists and 65 points. Knuble put in three more solid seasons with the Flyers, scoring over 20 goals in each season. In both 2007-08 and 2008-09, he played in all 82 games, helping the Flyers reach the playoffs on both occasions. In 2009, after the Flyers were eliminated in the first round, they signed high-profile defenseman Chris Pronger, creating a need for cap space. Since Knuble’s contract was already up anyway, it was decided not to re-sign him. Washington quickly signed him, as one of the glaring needs on the talented Capitals’ roster was a true power forward that could put up points, which Knuble has made a career out of doing. In his first 19 games as a Capital, Knuble scored 5 goals and 15 points, before he was sidelined with a broken finger.

Knuble has played for Team USA at 4 World Championships and the 2006 Turin Olympics.